Transcriptional regulation of gene expression, its timing, tissue distribution and response to both internal and environmental inputs, is a key link between the genome and phenotype. Variation in expression patterns across cell types is a primary determinant of tissue identity and function. Individual genetic variation in gene expression determines both our susceptibility to disease and provides the substrate for evolutionary adaptation. An integrated view of genome dynamics requires understanding these relationships in terms of genome organization. Toward this goal we will: Aim 3a. analyze publicly available gene expression data resources for physical correlates of tissue-specific gene expression patterns and for clustering of co-expression in LD domains and networks. Aim 3b. survey gene expression in 16 mouse strains using microarrays. The selected strains will include 'classical'inbred strains, inbred strains derived from M.m. musculus, M.m. domesticus, and M.m. castaneus origin, and inbred strains derived from hybrid origins. We will examine four tissues in mice of both sexes and relate our findings to genome organization and functional variation. Aim 3c. develop statistical methods and software for these analyses.